Insight into protein nuclear magnetic resonance research.

Nuclear magnetic resonance (NMR) is one of the most powerful techniques to investigate the geometry of molecules in solution. It has been widely applied, in recent years, to the study of protein conformation. However, full reconstruction of the 3-D structure of such macro-molecules, still constitutes a real challenge for the spectroscopist. Skills as diverse as biology, spectroscopy, signal processing, or computer sciences, are required. This paper presents various aspects of the research in that domain, and our contribution to it.

Alpha-cobratoxin: proton NMR assignments and solution structure.

The solution structure of alpha-cobratoxin, a neurotoxin purified from the venom of the snake Naja naja siamensis, at pH 3.2 is reported. Sequence-specific assignments of the NMR resonances was attained by a combination of a generalized main-chain-directed strategy and of the sequential method. The NMR data show the presence of a triple-stranded beta-sheet (residues 19-25, 36-41, and 52-57), a short helix, and turns. An extensive number of NOE cross peaks were identified in the NOESY NMR maps. These were applied as distance constraints in a molecular modeling protocol which includes distance geometry and dynamical simulated annealing calculations. A single family of structures is observed which fold in such a way that three major loops emerge from a globular head. The solution and crystal structures of alpha-cobratoxin are very similar. This is in clear contrast to results reported for alpha-bungarotoxin where significant differences exist.